Compounds which inhibit cytosolic phospholipase A2 and a process for making those compounds have been disclosed in U.S. Patent Publication No. 2003-0144282 A1, filed Nov. 22, 2002, the disclosure of which is incorporated by reference herein. These compounds are useful for a variety of purposes, including the relief of pain and inflammation. In order to bring a drug to market, it is necessary to have an economically feasible process for making the compound. Often, a process that works in the laboratory is not practical from a commercial standpoint. It would be desirable to have a relatively inexpensive and efficient method for making at least some of the aforesaid compounds.
Appleton, et al., in Tetrahedron Lett. 1993, 34, 1529, teach reductive C-3 alkylation of 3-unsubstituted indoles to produce C-3 functionalized indoles, especially 3-(arylmethyl)indoles and 3-(heteroarylmethyl)indoles. In the reference reaction, the initial indole is reacted with an aldehyde or ketone using triethylsilane and trifluoroacetic acid.
A solid-phase synthesis of indoles using palladium-catalyzed coupling of alkynes with iodoaniline derivatives is described by Fagnola, et al., Tetrahedron Letters, 38(13), 2307–2310 (1997).